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Recently, the less Shattering1 gene (SvLes1), an MYB transcription factor on chromosome V, in Setaria viridis, was reported to control the degree of seed shattering within S. viridis. SvLes1-1 and SvLes1-2 are the wild type (high shattering) allele and the reduced shattering allele, respectively. In addition to these two alleles, the loss-of-function allele through a transposable-element (TE) insertion in exon 2 was found in foxtail millet, a domesticated type of S. viridis, and was designated as SiLes1-TE. This gene is considered to be a domestication gene in foxtail millet. We screened 131 accessions of foxtail millet and found that 16 landraces (12.2%) of foxtail millet do not have the TE, despite expression of the non-shattering phenotype. We sequenced the SvLes1 gene of these 16 accessions and classified them into three alleles, SvLes1-1, SvLes1-2, and a new allele, SvLes1-3. The geographical distribution of these three alleles was different, suggesting that foxtail millet domestication and differentiation are more complex than expected.

In CheckMate 141, nivolumab significantly improved overall survival (OS) in patients with platinum-refractory recurrent or metastatic squamous cell carcinomas (R/M SCC) of the head and neck. However, reports on nivolumab for patients with non-SCC and/or a primary subsite excluded from CheckMate 141 are limited.We conducted a retrospective analysis of R/M head and neck cancer patients who received nivolumab. The study subject excluded patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx.A total of 59 patients were included, consisting of 40 males and 19 females with a median age of 61 years. Half of the patients had non-SCC histology. The main primary site included the sinonasal cavity (n = 18), salivary gland (n = 15), and nasopharynx (n = 13). Three (6.0%) patients achieved a complete response and 5 (10.0%) a partial response, giving an overall response rate (ORR) of 16.6%. Median time-to-treatment failure (TTF) and OS were 3.7 and 16.2 months, respectively. Salivary gland and nasopharyngeal cancer achieved relatively higher ORR (25.0 and 36.4%, respectively). On analysis by primary site, nasopharyngeal cancer showed a significantly better TTF and OS than the other primary sites. On analysis by histological findings, no significant difference in TTF and OS was observed between non-SCC and SCC.Nivolumab for cancers involving the salivary gland/nasopharynx and non-SCC histology showed comparable efficacy to that in CheckMate 141. This result indicates that nivolumab may be effective even for patients not included in CheckMate 141.

Significance Guinea yam is an important staple tuber crop in West Africa, where it contributes to the sustenance and sociocultural lives of millions of people. Understanding the genetic diversity of Guinea yam and its relationships with wild relatives is important for improving this important crop using genomic information. A recent genomics study proposed that Guinea yam originated from a wild relative, the rainforest species Dioscorea praehensilis . Our results based on sequencing of 336 Guinea yam accessions do not support this notion; rather, our results indicate a hybrid origin of Dioscorea rotundata from crosses between the savannah species Dioscorea abyssinica and D. praehensilis.

Significance Guinea yam is an important staple tuber crop in West Africa, where it contributes to the sustenance and sociocultural lives of millions of people. Understanding the genetic diversity of Guinea yam and its relationships with wild relatives is important for improving this important crop using genomic information. A recent genomics study proposed that Guinea yam originated from a wild relative, the rainforest species Dioscorea praehensilis. Our results based on sequencing of 336 Guinea yam accessions do not support this notion; rather, our results indicate a hybrid origin of Dioscorea rotundata from crosses between the savannah species Dioscorea abyssinica and D. praehensilis., White Guinea yam (Dioscorea rotundata) is an important staple tuber crop in West Africa. However, its origin remains unclear. In this study, we resequenced 336 accessions of white Guinea yam and compared them with the sequences of wild Dioscorea species using an improved reference genome sequence of D. rotundata. In contrast to a previous study suggesting that D. rotundata originated from a subgroup of Dioscorea praehensilis, our results suggest a hybrid origin of white Guinea yam from crosses between the wild rainforest species D. praehensilis and the savannah-adapted species Dioscorea abyssinica. We identified a greater genomic contribution from D. abyssinica in the sex chromosome of Guinea yam and extensive introgression around the SWEETIE gene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improving this crop through molecular breeding.

White Guinea yam (Dioscorea rotundata) is an important staple tuber crop of West Africa. However, its origin remains unclear. In this study, we re-sequenced 336 accessions of white Guinea yam and compared them with the sequences of the wildDioscoreaspecies using an improved reference genome sequence ofD. rotundata. Our results suggest a hybrid origin of white Guinea yam from crosses between the rainforest wild speciesD. praehensilisand the savannah-adaptedD. abyssinica. We identified a higher genomic contribution fromD. abyssinicain the sex chromosome of Guinea yam and an extensive introgression around theSWEETIEgene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improvement of this crop through molecular breeding.

Background It is important to consider that prolonged opioid use or opioid overuse for a patient who completed radiation therapy (RT) can have harmful effects. In 2018, pharmacists working with oncologists at outpatient clinics conducted an opioid de-escalation program for HNC patients who completed radiation therapy (RT) at the National Cancer Center Hospital East (NCCHE). The aim of this retrospective study was to evaluate the feasibility of a pharmacist-led opioid de-escalation (PLODE) program for HNC patients by comparing the outcomes of patients who participated in the PLODE program and those who did not. Methods This time-series analysis compared the outcomes of patients who participated in the PLODE program after CRT completion between June 2018 and February 2019 and those of patients who completed CRT between June 2017 and March 2018 and did not participate in the program. The PLODE program consisted of (1) number of opioid rescues, (2) patient’s complaints and (3) purpose of opioid use to patients based on the WHO Pain Ladder. Results Sixty-one patients completed CRT between June 2018 and February 2019. Of these 61 patients, 16 (26%) used opioids at the time of CRT completion and participated in the PLODE program. Ninety-three patients completed CRT between June 2017 and March 2018, and 32 patients (34%) used opioids at the time of CRT completion; these patients were evaluated as the control group. Patients who participated in the PLODE program discontinued opioids statistically earlier than those in the control group (median time to opioid discontinuation 11 days vs 24.5 days, HR 0.31, 95% CI 0.16-0.60, p Conclusions The study showed the feasibility of a PLODE program for HNC patients who completed CRT. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background In the CheckMate 141 trial, nivolumab, a human IgG4 anti-PD-1 monoclonal antibody, provided a significant improvement in overall survival (OS) of patients with recurrent or metastatic squamous cell carcinoma (SCC) of the oral cavity, pharynx, or larynx. In Japan, nivolumab has been approved for platinum pretreated head and neck cancers regardless of histologic type and subsite. In other words, nivolumab is also available for non-SCC and subsites of head and neck cancer which were not included in the CheckMate 141 trial. However, the efficacy of nivolumab for cancers arising from these other subsites has not been clarified. Methods: We retrospectively reviewed data for 122 consecutive patients with head and neck cancers treated with nivolumab in our institution between March 2017 and December 2018. Patients with head and neck SCC of oral, oropharyngeal, hypopharyngeal, and laryngeal cancer were excluded. Final analysis of the study population was restricted to those 37 patients with non-SCC histological type or SCC arising from other subsites of the head and neck. Results: Median age was 57 years (range 30 to 77). Primary sites were nasopharynx/sinonasal/salivary/other regions of the head and neck (n = 8/10/8/11). Nineteen patients had SCC and 18 had non-SCC. In patients who could be evaluated by RECIST (n = 32), objective response rate was 18.8% in the total study population, 37.5% in NPC, 10.0% in sinonasal cancer and 25.0% in salivary cancer. Median OS and time to treatment failure (TTF) in the total study population was 12.1 months and 2.3 months, respectively. Median TTF in NPC patients was better than that in patients with other primary sites (7.6 vs. 2.5 months, p = 0.016). There was a trend toward improved TTF in SCC group compared to non-SCC group (4.2 vs. 2.4 months, p = 0.31). Conclusion: Nivolumab showed favorable efficacy in head and neck cancers arising from subsites which were not included in the CheckMate141 trial, especially NPC patients.

The genomic sequences derived from rice centromeric regions were analyzed to facilitate the comprehensive understanding of the rice genome. A rice centromere-specific satellite sequence, RCS2/ TrsD/CentO, was used to screen P1-derived artificial chromosome (PAC) and bacterial artificial chromosome (BAC) genomic libraries derived from Oryza sativa L. ssp. japonica cultivar Nipponbare. Physical maps of the centromeric regions were constructed by DNA fingerprinting methods and the aligned clones were analyzed by end sequencing. BLAST analysis revealed the composition of genes, centromeric satellites and other repetitive elements, such as RIRE7/CRR, RIRE8, Squiq, Anaconda, CACTA and miniature inverted-repeat transposable elements. Fiber-fluorescent in situ hybridization analysis also indicated the presence of distinct clusters of RCS2/TrsD/CentO satellite interspersed with other elements, instead of a long homogeneous region. Several expressed genes, sequences representative of ancestral organellar insertions, relatively long simple sequence repeats (SSRs), and sequences corresponding to 5S and 45S ribosomal RNA genes were also identified. Thirty-one gene sequences showed high-similarity to rice full-length cDNA sequences that had not been matched to the published rice genome sequence in silico. These results suggest the presence of expressed genes within and around the clusters of RCS2/TrsD/CentO satellites in unsequenced centromeric regions of the rice chromosomes.

Rice, one of the world's most important food plants, has important syntenic relationships with the other cereal species and is a model plant for the grasses. Here we present a map-based, finished quality sequence that covers 95% of the 389 Mb genome, including virtually all of the euchromatin and two complete centromeres. A total of 37,544 non-transposable-element-related protein-coding genes were identified, of which 71% had a putative homologue in Arabidopsis. In a reciprocal analysis, 90% of the Arabidopsis proteins had a putative homologue in the predicted rice proteome. Twenty-nine per cent of the 37,544 predicted genes appear in clustered gene families. The number and classes of transposable elements found in the rice genome are consistent with the expansion of syntenic regions in the maize and sorghum genomes. We find evidence for widespread and recurrent gene transfer from the organelles to the nuclear chromosomes. The map-based sequence has proven useful for the identification of genes underlying agronomic traits. The additional single-nucleotide polymorphisms and simple sequence repeats identified in our study should accelerate improvements in rice production.

We constructed physical maps of rice chromosomes 1, 2, and 6-9 with P1-derived artificial chromosome (PAC) and bacterial artificial chromosome (BAC) clones. These maps, with only 20 gaps, cover more than 97% of the predicted length of the six chromosomes. We submitted a total of 193 Mbp of non-overlapping sequences to public databases. We analyzed the DNA sequences of 1316 genetic markers and six centromere-specific repeats to facilitate characterization of chromosomal recombination frequency and of the genomic composition and structure of the centromeric regions. We found marked changes in the relative recombination rate along the length of each chromosome. Chromosomal recombination at the centromere core and surrounding regions on the six chromosomes was completely suppressed. These regions have a total physical length of about 23 Mbp, corresponding to 11.4% of the entire size of the six chromosomes. Chromosome 6 has the longest quiescent region, with about 5.6 Mbp, followed by chromosome 8, with quiescent region about half this size. Repetitive sequences accounted for at least 40% of the total genomic sequence on the partly sequenced centromeric region of chromosome 1. Rice CentO satellite DNA is arrayed in clusters and is closely associated with the presence of Centromeric Retrotransposon of Rice (CRR)- and RIce RetroElement 7 (RIRE7)-like retroelement sequences. We also detected relatively small coldspot regions outside the centromeric region; their repetitive content and gene density were similar to those of regions with normal recombination rates. Sequence analysis of these regions suggests that either the amount or the organization patterns of repetitive sequences may play a role in the inactivation of recombination.

A basidiomycete, Coprinus sp. SF-1, was found to produce an L-Trp-oxidizing enzyme by screening from the culture collection of our laboratory. After solubilization by 1 M NaSCN from the particulate fraction of disrupted cells of the strain, the enzyme was purified about 76-fold to essential homogeneity. The enzyme had a molecular mass of about 420 kDa and the subunit molecular mass was 68 kDa. The enzyme contained 1 mol of non-covalently bound FAD per mol of the subunit. It catalyzed the simultaneous reactions of oxidative deamination and oxygenative decarboxylation of L-Trp to form indolepyruvic acid and indole-3-acetamide, the former of which was further oxidized to indole-3-acetic acid. The molar ratio of the respective reaction products was about 9:1. The enzyme specifically oxidized L-Trp, and slightly acted on L-Phe and L-Tyr. The Km for L-Trp was about 0.5 mM in both oxidase and oxygenase reactions. Thus, the enzyme is a novel one and was tentatively designated "L-Trp oxidase (deaminating and decarboxylating)". The optimum pHs of oxidase and oxygenase activities were 7.0 and 9.0, respectively. The optimum temperatures of both activities were 50 degrees C. The enzyme was stable at pH 6.0-10.5 and below 50 degrees C, and at 4 degrees C for 1 year.

This study was carried out to elucidate the prevalence of intestinal helminthic infections in rural communities in Nepal. Of 231 inhabitants randomly sampled in Kotyang and Judigaun, 140 (60.6%) were found to be infected with some soil-transmitted helminths. The highest prevalence was observed in hookworm infection (52.8%), followed by Trichuris trichiura (18.6%) and Ascaris lumbricoides (11.3%) infections. Some inhabitants harboured Vampirolepis nana and liver fluke. The female group aged 60 years old and more showed significantly higher T. trichiura infection rate than the male group with the same age (p

はじめに: 飲水の制限は, 透析の予後を左右する循環器系の合併症を予防する上で重要である. しかし, 透析を受けている患者の中には, この飲水制限が不良である者が少なくない. そこで, 透析患者における飲水制限とパーソナリティ上の関係について, MMPI (Minnesota Multiphasic Personality Inventory) を用いて調査した.対象と方法: 清湘会のクリニックにおいて慢性維持血液透析を受けている患者約398人のうち, 中-日の体重増加がdry weightの5%以上ある51名 (男性: 34名, 女性: 17名) を体重管理の不良な例 (不良群) とし, 中-日の体重増加がdry weightの3%以下の33名 (男性: 16名, 女性: 17名) を良好な例 (良好群) とした.これらの透析患者にMMPI (原法の新日本語版, 三京房, 京都) を施行し, 不良, 良好の2群の間で各尺度の平均値について男女別に集計を行い, 比較を行った. MMPIの日本での標準化に際して対象とした健常成人1,022名 (男性: 500名, 女性: 522名) との間でも比較を行った.結果: 不良群は良好群に比し, 不安, 身体的愁訴に関係する尺度 (Hs, D, Hy, Pdなど) で高い値をとる傾向が認められたが, 有意な差はなかった. 正常成人に比べると, 不良群, 良好群ともにL, Hs, D, Hy, Esの尺度で有意に高値を示した.考察: 今回示された不良群, 良好群にともに認められたHs, D, Hyの高値は, 透析患者の抑鬱状況と身体的拘りを示唆する. この3つの尺度の上昇はneurotic triadと呼ばれ, 透析患者の神経症的状態を示すものと考えられる. 有意差は認められなかったが, 不良群ではこれらの尺度の得点が良好群より高く, 神経症的傾向が強いようであった.追加尺度のEsの低値は自我の脆弱性に通じるもので, 透析を受ける患者の精神的脆さを示しているといえよう.

Stimulation of systemic antigen-specific IgE production plays an important role in the mediation of food allergy; however, the mechanism of IgE production against food antigens is not fully understood. The development of relevant animal models may help to elucidate the pathogenesis of food allergy. We here show that DBA/2 mice receiving a casein diet without any adjuvant produced high levels of IgE specific for casein, accompanied by predominant Th2-like responses in liver lymphocytes, mesenteric lymph node cells and spleen cells. This model of IgE production produced by feeding protein antigen as a constituent of the diet can be applied to investigate the mechanism of IgE production and to develop reagents for controlling food allergy.

We have investigated the effects of CP-99,994 [(+)-(2s,3s)-3-(2-methoxybenzylamino)-2-phenylpiperidine], a tachykinin NK1 receptor antagonist, HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and ketotifen (4-(1-methyl-4-piperidylidene)4 H-benzo[4,5]cycloheptal[1,2-b]thiophen-10(9H)-one hydrogen fumarate), a histamine H1 receptor antagonist with mast cell-stabilizing properties, on microvascular leakage induced by gaseous formaldehyde. Extravasation of Evans blue dye into airway tissues was used as an index of airway microvascular leakage. Leakage of dye in the trachea and main bronchi increased significantly in a concentration-dependent fashion after 10 min inhalation of formaldehyde (5-45 parts per million (ppm)). The airway response induced by 10 min inhalation of 15 ppm formaldehyde (trachea: 119.5 +/- 13.9 ng/mg, n = 7; main bronchi: 139.6 +/- 7.9 ng/mg, n = 7) was abolished by the administration of CP-99,994 (3 and 6 mg/kg i.v.), but not by the administration of HOE 140 (0.65 mg/kg i.v.) nor ketotifen (1 mg/kg i.v.). The increase in vascular permeability induced by formaldehyde in the rat airway was mediated predominantly by NK1 receptor stimulation. Activation of bradykinin receptors and mast cells did not appear to play an important role in this airway response.

This study was designed to investigate the patient's recognition of changes in facial profile due to orthognathic surgery. The results of questionnaires were summarized and analyzed in relation to cephalometric data.The subjects consisted of forty-three posttreatment patients (13 males and 30 females) with mandibular prognathism, , who had undergone orthognathic surgery at Hiroshima University Dental Hospital. In this study, patient's recognition of improvement in facial profile was summarized in relation to morphologic changes associated with orthognathic surgery by means of Spearman's correlation analysis.The results were as follows:1. Before treatment, eighty-eight percent of patients were anxious about disharmony of the facial profiles, and the degree of anxiousness was severe in half of them. As for facial areas, the lower lip and chin were their greatest concern.2. After treatment, eighty-four percent of patients recognized improvement in facial profile, and sixty-three percent of patients assessed that their profiles were improved more substantially than expected before treatment. As for facial parts, more than seventy percent of patients mainly recognized improvement in lower lip and chin.3. The patient's recognition of improvement in facial profile, especially chin, exhibited a significantly positive correlation with the amount of mandibular setback during treatment.These results suggested that most patients assessed that improvement in facial profile was achieved by orthognathic surgery. It is shown that their recognition of improvement in their facial profiles is significantly correlated with the amount of mandibular setback.

Rice (Oryza sativa L.) is a model organism for the functional genomics of monocotyledonous plants since the genome size is considerably smaller than those of other monocotyledonous plants. Although highly accurate genome sequences of indica and japonica rice are available, additional resources such as full-length complementary DNA (FL-cDNA) sequences are also indispensable for comprehensive analyses of gene structure and function. We cross-referenced 28.5K individual loci in the rice genome defined by mapping of 578K FL-cDNA clones with the 56K loci predicted in the TIGR genome assembly. Based on the annotation status and the presence of corresponding cDNA clones, genes were classified into 23K annotated expressed (AE) genes, 33K annotated non-expressed (ANE) genes, and 5.5K non-annotated expressed (NAE) genes. We developed a 60mer oligo-array for analysis of gene expression from each locus. Analysis of gene structures and expression levels revealed that the general features of gene structure and expression of NAE and ANE genes were considerably different from those of AE genes. The results also suggested that the cloning efficiency of rice FL-cDNA is associated with the transcription activity of the corresponding genetic locus, although other factors may also have an effect. Comparison of the coverage of FL-cDNA among gene families suggested that FL-cDNA from genes encoding rice- or eukaryote-specific domains, and those involved in regulatory functions were difficult to produce in bacterial cells. Collectively, these results indicate that rice genes can be divided into distinct groups based on transcription activity and gene structure, and that the coverage bias of FL-cDNA clones exists due to the incompatibility of certain eukaryotic genes in bacteria.

We constructed physical maps of rice chromosomes 1, 2, and 6-9 with P1-derived artificial chromosome (PAC) and bacterial artificial chromosome (BAC) clones. These maps, with only 20 gaps, cover more than 97% of the predicted length of the six chromosomes. We submitted a total of 193 Mbp of non-overlapping sequences to public databases. We analyzed the DNA sequences of 1316 genetic markers and six centromere-specific repeats to facilitate characterization of chromosomal recombination frequency and of the genomic composition and structure of the centromeric regions. We found marked changes in the relative recombination rate along the length of each chromosome. Chromosomal recombination at the centromere core and surrounding regions on the six chromosomes was completely suppressed. These regions have a total physical length of about 23 Mbp, corresponding to 11.4% of the entire size of the six chromosomes. Chromosome 6 has the longest quiescent region, with about 5.6 Mbp, followed by chromosome 8, with quiescent region about half this size. Repetitive sequences accounted for at least 40% of the total genomic sequence on the partly sequenced centromeric region of chromosome 1. Rice CentO satellite DNA is arrayed in clusters and is closely associated with the presence of Centromeric Retrotransposon of Rice (CRR)- and RIce RetroElement 7 (RIRE7)-like retroelement sequences. We also detected relatively small coldspot regions outside the centromeric region; their repetitive content and gene density were similar to those of regions with normal recombination rates. Sequence analysis of these regions suggests that either the amount or the organization patterns of repetitive sequences may play a role in the inactivation of recombination.

Measurements of %Fat, nutrient intake and maximal aerobic power (MAP) were carried out on Nepalese to clarify the cause of obesity attended with modernization. One hundred thirty-two males (KV) who have a natural living style, 20-84 years of age, in rural district and 237 males who have a living style affected by the rapid urbanization, in surburban district were selected as subjects. The subjects of surburban district were divided into two groups. One of them included 147 farmers (BF) who engage in not mechanized farming, 20-73 years of age. Another group included 90 students and wage laborers (BNF) who go to and from Kathmandu (the capital of Nepal), 20-57 years of age. %Fat was estimated from skinfold thickness according to the method of Nagamine (1975). The survey for the nutrient intake was carried out by the 24-hour recall method to obtain the individual food consumption using the food models. Measurement of MAP was made indirectly by the modified of Margaria et al (1965). The main results are summarized as follows. 1) Mean %Fat and the appearance rates of obesity in each age group showed high values in following order: BNF greater than BF greater than KV. 2) Mean caloric intake in KV was higher than those in BF and in BNF an almost all age groups and no significant difference was found between BF and BNF in all age groups. 3) No significant differences in mean fat intake and in mean animal fat intake among all groups were found in almost all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

An assay of apolipoproteins (Apo) C-II, C-III and E in human sera by single radial immunodiffusion (SRID) is described. The procedure involves pretreatment of the serum sample with surfactant to facilitate diffusion of very low density lipoproteins in agarose. This allowed measurement of apolipoproteins in lipidemic sera by SRID in agarose gel. The intraplate coefficient of variation was less than 2.5%, and the interplate coefficient of variation, less than 3.0%. Correlation with double-antibody radioimmunoassay produced the following coefficients of correlation: gamma = 0.9931 (n = 17) for Apo C-II, gamma = 0.9221 (n = 33) for Apo C-III, and gamma = 0.9340 (n = 17) for Apo E.